Observations on the decrease in antibody response and protective immunity of bacterial polysaccharide vaccine having smaller molecular size, indicate the correlation between the molecular size of PS and immunogenicity of vaccines. To study the effect of molecular size of PS on the immunogenicity, pneumococcal type 3 PS was treated with 0.5-1 N hydrochloric acid for 0.5, 1 and 2 hrs., to prepare various size of PS with Kd values, 0.23 to 0.80. The dose-response patterns of these type 3 PS fractions were analyzed by plaque-forming cell assay. Initial results indicate that the low magnitude of immune response was induced by the PS sample having small molecular size. Their effectiveness in inducing low- dose paralysis will be examined. The different size PS or oligosaccharide were conjugated with the inactivated 19F pneumolysin and the antibody response was determined. The results showed that the serum levels of 19F IgG1 and IgG3 were significantly higher in mice immunized with a conjugate, in which large molecular size of PS was used to prepared the conjugate, than the group injected with a conjugate, in which small molecular size of OS was used.